CONTROL OF UTERINE STROMAL MITOSIS IN RELATION TO UTERINE SENSITIVITYAND DECIDUALIZATION IN MICE

The relationship between mitosis, ovarian hormones, decidual stimuli a nd decidualization was investigated using progestagen-treated ovariect omized mice. Oestradiol, or the intraluminal instillation of oil or sa line, all stimulated stromal mitosis. When oil or saline was instilled following oestradiol, the response depended on the dose of oestradiol , the interval between the oestradiol and the instillation, and the ti me when the mice were killed. After 20 ng oestradiol, the instillation of oil 7 h later induced large mitotic and decidual responses that we re evident within 17 h of instillation and increased with time. Smalle r mitotic and decidual responses were obtained when the interval betwe en oestradiol and oil was 24 h; there was no response when the interva l was 42 h. When a higher dose (100 ng) of oestradiol was given, oil i njected 7 h later initially stimulated mitosis (at 17 h), but this eff ect was reduced at 24 h and no decidualization occurred. After instill ing oil 24 or 42 h after 100 ng oestradiol, the mitotic response was l imited, and there was no decidual response. Regardless of the dose of oestradiol, saline induced only a transient mitotic response and no de cidualization occurred. It is concluded that there are three stimuli t hat can cause stromal mitosis in the progestagen-treated mouse uterus: oestrogen, an intraluminal stimulus (blastocyst, oil or saline) and f actors associated with decidualization. Oestradiol not only induces mi tosis, but also produces a period of heightened sensitivity to the mit otic effects of intraluminal stimuli. In addition, low doses of oestra diol induce a period of sensitivity to decidual stimuli. When these ph ases of uterine sensitivity to intraluminal stimuli have passed, decid ualization and mitosis within the stroma can continue, presumably stim ulated by local signals from the decidua in a self-propagating cascade of cellular proliferation and differentiation.